tbuckley/cabot-search huggingface dataset:
INSP-11. Patient-centered monitoring and care of cognitive late effects in pediatric brain tumor survivors with and without Cerebellar Mutism Syndrome (CMS).
Authors: Karin Walsh, Maegan Sady, Kaitlyn Tiplady, Shawna van Scoyoc, Hannah Weisman, Kristina Hardy
Journal: Neuro-Oncology (2022)

Abstract Risks of cognitive late effects in children with brain tumors is well-established. However, group heterogeneity may limit generalizability and result in inadequate neurocognitive monitoring and care. Children with CMS have unique long-term cognitive risks and current knowledge may not adequately describe their experience or needs. The establishment and implementation of patient-centered, empirically-derived assessment of cognitive change following tumor diagnosis and treatment is a novel, precision-based approach to patient care. METHODS: 30 patients diagnosed with posterior fossa tumor who had at least 2 neuropsychological evaluations were included. Primary outcomes were processing speed (Wechsler PSI) and working memory (WMI). Secondary outcomes were verbal and nonverbal intellect. Reliable change indices (RCIs) were computed (Chelune et al., 1993). Using an 80% CI, 10% would be expected to decline, while 90% would stay stable or improve. RESULTS: Mean age in the full sample was 9.2 (3.32) years at T1 and 13.0 (4.11) years at T2, with an average of 2.7 (2.58) years between assessments. Males made up 56.7% of the sample. Five of the 30 (17%) were CMS+. The CMS+ patients were similar in age to CMS- patients, were predominantly male (80%), and mostly received photon radiation (60%). The full sample showed greater prevalence of declining verbal (21%), spatial (58%) and working memory (29%) functions than the expected (10%). The CMS+ group had higher rates of processing speed (50% v. 7%) and working memory (50% v. 27%) declines than the CMS- group. In contrast, the CMS- group appeared to show more prevalent declines in spatial reasoning than the CMS+ group (67% v. 33%). CONCLUSIONS: There appear to be unique domains impacted in the CMS+ group, which can convey specific long-term outcomes specific to this subgroup of patients. These results highlight the utility of individualized, empirically-driven analysis of change in cognitive functioning in this patient population.
Molecular profiles of gastric adenocarcinoma among Hispanic patients at a safety-net healthcare system.
Authors: Huili Zhu, Yvonne Sada, Ramon Jin
Journal: Journal of Clinical Oncology (2022)

e16067 Background: Hispanic patients with gastric cancer are more likely to have advanced stage at diagnosis, signet ring histology, and worse survival outcomes than non-Hispanic patients. Although socioeconomic factors may contribute to these disparities, the molecular biology of gastric cancer in Hispanic patients has not been well characterized. Hispanic patients comprise &lt; 0.05% of gastric adenocarcinoma cases in The Cancer Genome Atlas (TCGA). Methods: We conducted a retrospective study of patients with gastric adenocarcinoma diagnosed between January 2019 to January 2022 at a safety net hospital in Houston, Texas. The hospital serves a patient population of which 91% are racial/ethnic minorities and 57% are Hispanic. Next generation sequencing data was obtained via Tempus|xT tissue assay (DNA sequencing of 648 genes in tumor and matched normal samples at 500x depth) and/or Tempus|xF liquid biopsy assay (ctDNA sequencing of 105 genes in peripheral blood samples at 5,000x depth) for germline and/or somatic mutations. We compared mutation findings in Hispanic vs non-Hispanic patients. Results: Among 56 patients with gastric adenocarcinoma, 45 (80%) were Hispanic, 11 (20%) were non-Hispanic White, Black, or other, 30 (54%) were male, median age was 54±13, and 14 (25%) were younger than 50 years old. The majority were metastatic (65%), and 6 (11%) were signet ring cell subtype. The most common pathogenic somatic variants across the entire cohort included: TP53 (55%) , CDH1 (34%) , ARID1A (25%) , LRP1B (20%) , RHOA (16%) , SMAD4 (16%) , ERBB2 (14%) , KRAS (14%) , CDKN2A (12%), and PIK3CA (12%). Microsatellite instability was found in 1 (0.02%) patient. Somatic CDH1 mutations were present in 15 (33%) Hispanic patients, of whom 7 were younger than 50 years old, and 2 (18%) non-Hispanic patients. Germline CDH1 mutations was identified in 1 Hispanic patient. TP53 mutations occurred in 14 (31%) Hispanic patients and 6 (55%) non-Hispanic patients. Conclusions: CDH1 mutations, which are associated with familial gastric cancers and more aggressive disease, were present in 33% of Hispanic patients with gastric adenocarcinoma in our study. Nearly half of these identified patients were younger than 50 years old. The high frequency of CDH1 mutations may contribute to the unique pathogenesis of gastric cancers in Hispanic patients.
A randomized phase II study of gemcitabine and nab-paclitaxel compared with 5-fluorouracil, leucovorin, and liposomal irinotecan in older patients with treatment-naïve metastatic pancreatic cancer (GIANT): ECOG-ACRIN EA2186—Trials in progress.
Authors: Efrat Dotan, Paul J. Catalano, Leon Lenchik, Robert Boutin, Xin Yao, Shaalan Shaalan Beg, Namrata Vijayvergia, Constantine Gatsonis, David Bing Zhen, Daneng Li, Lynne I. Wagner, Melissa A. Simon, Terence Z. Wong, Peter J. O'Dwyer
Journal: Journal of Clinical Oncology (2022)

TPS4185 Background: Evidence-based data is lacking to guide the care of older adults with newly diagnosed metastatic pancreatic cancer (mPCA). As a result, treatment approach and the selection of chemotherapy regimens are often extrapolated from data from younger patients. Furthermore, vulnerable older adults are often treated with dose adjusted regimens with limited data to support this practice. EA2186 is a phase II randomized controlled trial, and the first prospective study aiming to define the optimal treatment approach of vulnerable older adults with newly diagnosed mPCA. Methods: Patients aged 70 years and over with histologically confirmed pancreatic adenocarcinoma, evidence of metastatic disease, ECOG PS 0-2 and adequate organ function, who are considered vulnerable are eligible for this trial (accrual target 184). This study utilizes a screening geriatric assessment which characterize patients as fit, vulnerable or frail by evaluating functional status, cognition and co-morbidities. Vulnerable patients according to this screening assessment are those with mild abnormalities in functional status, comorbidities and/or cognition, or older than 80 years of age. Those patients will be randomized to receive either modified Gemcitabine/Nab-Paclitaxel or dose-reduced 5-Fluorouracil Leucovorin and Liposomal Irinotecan every 2 weeks. A comprehensive geriatric assessment (GA) and quality of life (QOL) evaluation are completed prior to initiation of therapy for all randomized patients. Follow up will continue until disease progression or withdrawal, with repeated GA and QOL assessments at each disease evaluation. Overall survival is the primary objective, with secondary objectives including progression free survival, and response rate. Enrolled patients will be stratified by age 70-74 vs ≥75, and ECOG PS 0-1 vs 2. Additional endpoints of interest for older adults include: evaluation of risk factors identified through GA, and capturing toxicities of interest for this patient population (i.e. hospitalization, deterioration in PS, and falls). Correlative studies include assessment of pro-inflammatory biomarkers or aging in the blood (IL-6 and CRP) as well as imaging evaluation of sarcopenia and body composition as predictors of treatment tolerance. Clinical trial information: NCT04233866.
The efficacy and safety of IBI314 on delta and omicron variant of SARS-CoV-2: First-in-human evidence
Authors: Ling Sang, Bo Cheng, Yuheng Yu, Yin Xi, Yun Wang, Bingdong Fan, Jijie Li, Jingtao Dai, Guifen Gan, Shijun Tong, Bin Sun, Xiaojing Qi, Wenhua Liang, Jianxing He, Nanshan Zhong
Journal: Journal of Infection (2022)
Phase 3, randomized, placebo-controlled study of stereotactic body radiotherapy (SBRT) with or without pembrolizumab in patients with unresected stage I or II non–small cell lung cancer (NSCLC): KEYNOTE-867.
Authors: Salma K. Jabbour, Baerin Houghton, Andrew George Robinson, Xavier Quantin, Thomas Wehler, Dariusz Kowalski, Myung-Ju Ahn, Mustafa Erman, Giuseppe Giaccone, Hossein Borghaei, Jessica McLean, Yan Xu, Fabricio Souza, Georg Pall
Journal: Journal of Clinical Oncology (2022)

TPS8597 Background: Anti–PD-(L)1-directed therapy following radiotherapy or following concurrent chemoradiation is associated with significantly longer PFS and OS in patients with advanced or metastatic NSCLC, including those with locally advanced inoperable tumors. KEYNOTE-867 (NCT03924869) evaluates the efficacy and safety of SBRT with or without pembrolizumab in patients with unresected stage I or II NSCLC. Methods: In this phase 3, randomized, placebo-controlled study, approximately 530 adult patients with previously untreated, unresected, histologically/cytologically confirmed stage I or II (T1 to limited T3, N0, M0) NSCLC are randomized 1:1 to receive thoracic SBRT to primary tumors for ≤2 wk (Table) and either pembrolizumab 200 mg or placebo every 3 wk for 17 cycles (approximately 1 year) or until disease recurrence, development of unacceptable AEs, SBRT not started for any reason, or study withdrawal. Randomization is stratified by disease stage (I vs II), ECOG PS (0 or 1 vs 2), geographic region (East Asia vs non-East Asia), and reason for not receiving surgery (medically inoperable vs refused surgery). Imaging assessment by blinded independent central review (BICR) occurs at 12 wk (≥10 wk after SBRT completion), followed by every 16 wk for 3 y, and then every 6 mo. Primary endpoints are event-free survival (EFS) by BICR and OS. Secondary endpoints include time to death or distant metastases and safety; exploratory endpoints are time to subsequent treatment, disease-specific survival, and time to recurrence/progression on subsequent line of therapy. AEs are monitored throughout the trial until 30 d after last dose (90 for serious AEs) and graded according to NCI CTCAE version 4.0. EFS and OS are analyzed by the nonparametric Kaplan-Meier method, treatment differences by stratified log-rank test, and hazard ratios by stratified Cox proportional hazard model with Efron's method of tie handling. Enrollment started on June 17, 2019, and is ongoing at 168 sites around the world. Clinical trial information: NCT03924869. [Table: see text]
Minimal residual disease-guided stop and start of venetoclax plus ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia (HOVON141/VISION): primary analysis of an open-label, randomised, phase 2 trial
Authors: Arnon P Kater, Mark-David Levin, Julie Dubois, Sabina Kersting, Lisbeth Enggaard, Gerrit J Veldhuis, Rogier Mous, Clemens H M Mellink, Anne-Marie F van der Kevie-Kersemaekers, Johan A Dobber, Christian B Poulsen, Henrik Frederiksen, Ann Janssens, Ida Schjødt, Ellen C Dompeling, Juha Ranti, Christian Brieghel, Mattias Mattsson, Mar Bellido, Hoa T T Tran, Kazem Nasserinejad, Carsten U Niemann
Journal: The Lancet Oncology (2022)
RARE-07. Low resting energy expenditure is associated with clinical and radiological hypothalamic damage in children surviving a suprasellar brain tumor
Authors: Jiska van Schaik, Marcella Burghard, Maarten Lequin, Emiel van Maren, Anne van Dijk, Tim Takken, Lineke Rehorst, Boudewijn Bakker, Lisethe Meijer, Eelco Hoving, Netteke Schouten- van Meeteren, Marta Fiocco, Wim Tissing, Hanneke van Santen
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Children with suprasellar brain damage are at risk for hypothalamic dysfunction (HD). HD may lead to decreased resting energy expenditure (REE) contributing to the development of hypothalamic obesity. Decreased REE, however, is not present in all children with hypothalamic damage. Our aim was to assess which children suspect for HD have low REE, and if REE outcome can be associated with clinical severity of HD or with radiological posterior hypothalamic damage. METHODS: A retrospective cohort study was performed evaluating all children diagnosed with brain injury at risk for HD in whom REE measurement was performed. Measured REE (mREE) was compared to predicted REE (pREE) using amongst others the Schofield equation. Low REE was defined as mREE&amp;lt;90% compared to pREE. Radiologic hypothalamic damage was scored using Muller grading score. The mREE/pREE quotient was associated to a clinical score for HD symptoms and to radiological hypothalamic damage. RESULTS: Sixty-seven children suspected for HD (94% brain tumor diagnosis) with a mean BMI SDS of +2.3 ± 1.0 were included. Of these, 45 (67.2%) had mREE &amp;lt;90% compared to the pREE. Children with severe HD symptoms had a significant lower mean mREE/pREE quotient compared to children with no, mild, or moderate HD symptoms. Mean mREE/pREE quotient of children with posterior hypothalamic damage was significantly lower compared to children with no damage or with anterior damage. Tumor progression or tumor recurrence, severe clinical HD, and panhypopituitarism with DI were significant risk factors for reduced REE. CONCLUSION: Not all children suspect for HD have a low REE. Low REE is associated with clinical and radiological scores for hypothalamic damage. REE measurements in childhood brain tumor survivors may be useful to distinguish between those who may benefit from obesity treatment that increases REE from those who would be better helped using other obesity interventions.
HGG-30. H3.3 G34R/V mutations disrupt H3.3 mitotic phosphorylation leading to high-grade glioma formation through the induction of chromosomal instability
Authors: Charles Day, Florina Grigore, Faruck Hakkim, Alyssa Langfald, Edward Hinchcliffe, James Robinson
Journal: Neuro-Oncology (2022)

Abstract Pediatric high-grade gliomas (pHGG) are among the most lethal of all human cancers. Histone H3.3 G34R/V mutations are an early event in these tumors and show reduced H3.3 K36 trimethylation; implicating epigenetic dysregulation in tumorigenesis. Here we present evidence that H3.3 G34R/V mutations promote tumor formation via the induction of chromosomal instability (CIN). Pericentromeric H3.3 is phosphorylated at S31 by Chk1 during mitosis. We observed that the H3.3 G34R mutation reduced Chk1 phosphorylation of H3.3 S31 by &amp;gt;90% in vitro. Furthermore, H3.3 G34 mutant cells have reduced pericentromeric H3.3 S31 phosphorylation in mitosis compared to WT H3.3 cell lines. H3.3 G34 mutant pHGG cells also have significantly elevated rates of CIN as compared to H3.3 WT cells. Overexpression of H3.3 G34R, G34V or non-phosphorylatable S31A in H3.3 WT, diploid cells caused a significant increase in CIN, but H3.3 K36M overexpression had no effect on chromosome segregation. These studies demonstrate that H3.3 G34R/V mutations are sufficient to induce CIN in normal, diploid cells. To determine if this process contributes to tumorigenesis, we used RCAS Nestin-TVA mice to overexpress H3.3 WT, G34R, or S31A – P2A-linked to PDGFB in glial precursor cells of newborn mice. Over 100 days, S31A and G34R mice had drastically reduced survival (averaging 77, 81, and 100 days for S31A, G34R, and WT). Furthermore, most G34R and S31A mice developed HGG, while H3.3 WT mice remained tumor-free. Our work implicates CIN as a driver of H3.3 G34 mutant pHGG formation.
INSP-12. Molecular architecture of the human brain and brain cancer
Authors: Sten Linnarsson
Journal: Neuro-Oncology (2022)

Abstract Single-cell gene expression analysis has revolutionized biomedical research, leading to comprehensive atlases of human tissues, insights into development and homeostasis and allowed highly multiplexed perturbations with cell type specificity. Here, I present our comprehensive single-cell atlas of the human nervous system, both in development and in the adult. We describe unexpected regional diversity among human glial cell types, with implications for regions-specific glial brain disease. However, in single-cell analysis, spatial context is lost, complicating the analysis of cell-cell interactions, spatial gradients and patterns of cell distribution. Spatial methods of gene expression analysis have therefore increased in importance, and are currently a very active are of research and development. We have developed a scalable and highly multiplexed method of spatial gene expression analysis based on electrophoretic capture of mRNA. I showcase its throughput and robustness by presenting complete spatial atlases of the adult mouse brain, as well as the whole developing human head at 7 weeks post-conception. Furthermore, I will discuss our ongoing work to apply these methods to human glioblastoma in order to reveal the spatial architecture of this devastating tumor.
Let our patients shine: Survivorship and health interventions in nutrition and exercise program for breast cancer survivors.
Authors: Eleonora Teplinsky, Jessica Cording, Elizabeth Horowitz, Elena I Fishman, Amanda Podolski, Moira Katherine Christoudias, Donald Tomaszewski, Robert Angner, Laura Klein
Journal: Journal of Clinical Oncology (2022)

e24032 Background: Nutrition and lifestyle interventions are instrumental in modifying cancer risk. These changes are often challenging for patients to make due to residual side effects from active treatment and/or ongoing toxicities from current treatment. The SHINE (Survivorship and Health Interventions in Nutrition and Exercise) Program is a wellness program for patients with breast cancer focusing on three pillars of nutrition, exercise and community in order to improve overall health outcomes and decrease the risk of cancer recurrence. Methods: Participants in SHINE have either been diagnosed with ductal carcinoma in situ (DCIS) and/or stage I-IV breast cancer. They are referred to the program at the three-month breast surgery post-operative follow-up appointment or any time after that. All patients are referred to meet with a registered dietitian (RD) and integrative health coach, who provides counseling and education on how to reduce risk through diet and lifestyle, using evidence-based recommendations. Patients are provided with support and accountability. A collaborative program, the Physician Referred Exercise Program (PREP), was established with our health system’s medical fitness center, Valley Health LifeStyles. Patients undergo a fitness assessment that focuses on aerobic fitness, muscle strength and endurance, flexibility, &amp; functional activity. Each patient then receives an exercise prescription developed by a degreed exercise specialist, taking into account both the physician’s &amp; patient’s recommendations &amp; goals. Results: Each component of the SHINE Program has been developed in various stages due to the COVID-19 pandemic. 336 patients with either DCIS or stage I-IV breast cancer have been seen by the RD from December 2020 through January 2022. Mean number of visits/patient: 1.89 (range 1-8). N = 48 were participants in a 12-week study on the feasibility of nutrition counseling and impact on quality of life (QOL) which is still in progress. 76 patient referrals have been placed to the PREP program from August 2021-February 2022. Multiple community programs (Table) have been created for patients to help them develop shared experiences &amp; camaraderie with each other so that they can better integrate new ideas and lifestyle modifications. Conclusions: The SHINE Program addresses care for the whole person, empowering individuals to live their healthiest lifestyle. Future work will focus on clinical trials to evaluate the benefits of these individual and collective interventions on overall QOL, QOL subscales (physical, psychological, social &amp; spiritual well-being), &amp; survivorship symptoms.[Table: see text]
AYA rhabdomyosarcoma: Evolving changes in regional service delivery impacting on outcomes and meningeal disease.
Authors: Helen Hatcher, Han Wong, Jenny Harrington, Sarah Prewett, Gail Horan
Journal: Journal of Clinical Oncology (2022)

e22006 Background: Rhabdomyosarcoma (RMS) is a rare and aggressive sarcoma with a variable prognosis dependent upon age, histology, PAX-FOXO1 translocation status, site, stage of disease and treatment. RMS has a peak age of incidence in adolescents and young adults (AYA). Centralisation of care in the UK has impacted on treatments given and outcome. With extended outcomes in an age associated with poor prognosis we have seen increased rates of meningeal disease as a late event. We examined factors predisposing to meningeal involvement and associated outcomes in changing treatments. Methods: Retrospective review of AYA with RMS, treated between 2004 and 2022 at a regional AYA center serving a population of 2.5 million. Results: 17 patients (9 males, 8 females) were identified (median age 18). At diagnosis, 5 patients had locally advanced disease and 11 had metastases. Meningeal disease developed in 11/17 after a median of 11 months (range 6-87) from diagnosis. Overall survival was 14 months (range 14-87) for those who developed meningeal disease versus 54 months (range 6-167, not reached in 3) in those who did not. Following meningeal involvement, survival ranged from 0-7+ months. Histology of those with meningeal disease: embryonal (5) alveolar (6). 5/6 patients with alveolar RMS (ARMS) had FOXO1 gene rearrangement. Presentation of meningeal disease included: headaches (7), visual phenomena (3), nausea/vomiting (2), unusual chest or back pain (5). Risk factors included bone marrow infiltration (2/2), para-meningeal/orbital primary (4/4), and widespread metastatic or locally advanced primary disease 10/11. 10/11 received treatment with radiotherapy and/or chemotherapy with symptomatic benefit. Conclusions: Meningeal disease in RMS occurs more frequently in those with a primary close to the brain and with bone marrow involvement. Site and extent of primary disease was more predictive than histology for meningeal disease, but not of survival. Adaptation to longer initial treatments with maintenance therapy has increased survival in AYA RMS. Early recognition of key warning symptoms is important to guide prognostication and symptom control.